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STAT5b is required for GH-induced liver IGF-I gene expression
H W Davey1, T Xie, M J McLachlan
1AgResearch, Ruakura Research Centre, Hamilton 2001, New Zealand. helen.davey@agresearch.co.nz
Endocrinology
|August 23, 2001
Summary
Growth hormone (GH) stimulates liver Insulin-like Growth Factor-I (Igf-I) expression. The Janus kinase-signal transducer and activator of transcription 5b (JAK2-STAT5b) pathway is crucial for this GH-induced Igf-I gene expression in the liver.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Growth hormone (GH) is known to increase Insulin-like Growth Factor-I (Igf-I) expression in the liver.
- The specific intracellular signaling pathways mediating this GH effect remain largely unidentified.
- The Janus kinase-signal transducer and activator of transcription 5b (JAK2-STAT5b) pathway is activated by GH and influences sexually dimorphic growth and liver cytochrome P450 expression.
Purpose of the Study:
- To investigate the role of STAT5b in the GH-mediated activation of Igf-I gene expression in the liver.
- To determine if STAT5b is essential for GH to induce Igf-I mRNA in mouse liver.
Main Methods:
- Utilized wild-type and Stat5b(-/-) mice.
- Stimulated hypophysectomized male mice with exogenous pulses of GH.
- Monitored the induction of Igf-I mRNA in liver tissue.
Main Results:
- GH successfully induced liver Igf-I mRNA expression in wild-type mice.
- GH failed to induce liver Igf-I mRNA expression in Stat5b(-/-) mice.
- Stat5b(-/-) mice maintained normal GH receptor expression and showed GH induction of Cytokine-inducible SH2 protein (Cis).
Conclusions:
- STAT5b plays a critical and specific role in the GH-induced expression of the Igf-I gene in the liver.
- The absence of STAT5b prevents GH from stimulating Igf-I mRNA production, despite intact GH signaling components like the receptor and Cis induction.